The road to systemic therapy in von Hippel-Lindau (VHL) disease: Are we there yet?

Shepherd, Scott T.C.; Drake, William M; Turajlic, Samra

doi:10.1016/j.ejca.2022.12.011

Cited by 5 publications

(1 citation statement)

References 40 publications

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“…Of those, only the VHL variant occurred in a patient, previously untested, but fulfilling the criteria for genetic testing. Interestingly, this variant was therapeutically actionable (OncoKB level 3B), but target drugs are not universally available (only Food and Drug Administration (FDA)-approved) [ 45 , 46 ]. All the others pathogenic variants were from patients not meeting criteria for germline testing for the specific genes, but their identification uncovered an underlying hereditary cancer predisposition.…”

Section: Discussionmentioning

confidence: 99%

Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort

Vanni,

Pastorino,

Andreotti

et al. 2024

J Transl Med

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Background Comprehensive next-generation sequencing is widely used for precision oncology and precision prevention approaches. We aimed to determine the yield of actionable gene variants, the capacity to uncover hereditary predisposition and liquid biopsy appropriateness instead of, or in addition to, tumor tissue analysis, in a real-world cohort of cancer patients, who may benefit the most from comprehensive genomic profiling. Methods Seventy-eight matched germline/tumor tissue/liquid biopsy DNA and RNA samples were profiled using the Hereditary Cancer Panel (germline) and the TruSight Oncology 500 panel (tumor tissue/cfDNA) from 23 patients consecutively enrolled at our center according to at least one of the following criteria: no available therapeutic options; long responding patients potentially fit for other therapies; rare tumor; suspected hereditary cancer; primary cancer with high metastatic potential; tumor of unknown primary origin. Variants were annotated for OncoKB and AMP/ASCO/CAP classification. Results The overall yield of actionable somatic and germline variants was 57% (13/23 patients), and 43.5%, excluding variants previously identified by somatic or germline routine testing. The accuracy of tumor/cfDNA germline-focused analysis was demonstrated by overlapping results of germline testing. Five germline variants in BRCA1, VHL, CHEK1, ATM genes would have been missed without extended genomic profiling. A previously undetected BRAF p.V600E mutation was emblematic of the clinical utility of this approach in a patient with a liver undifferentiated embryonal sarcoma responsive to BRAF/MEK inhibition. Conclusions Our study confirms the clinical relevance of performing extended parallel tumor DNA and cfDNA testing to broaden therapeutic options, to longitudinally monitor cfDNA during patient treatment, and to uncover possible hereditary predisposition following tumor sequencing in patient care.

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Section: Discussionmentioning

confidence: 99%

Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort

Vanni,

Pastorino,

Andreotti

et al. 2024

J Transl Med

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Stereotactic Radiosurgery for Hemangioblastomas

Park,

Yoo,

Windisch

et al. 2024

Adult CNS Radiation Oncology

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Belzutifan in Individuals with von Hippel-Lindau Retinal Hemangioblastomas: Institutional Experience and Review of the Literature

Jamshidi,

Lozano,

Tucker

et al. 2024

Ocul Oncol Pathol

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Introduction: The systemic HIF-2 alpha inhibitor, belzutifan, has been approved for use in patients with VHL-associated renal cell carcinoma, central nervous system (CNS) hemangioblastomas, and pancreatic neuro-endocrine tumors. This drug has also shown promise in controlling VHL retinal hemangioblastomas (RH), but little work has been published on the use of the drug in this setting. Methods: We conducted a retrospective review of patients with VHL-associated RH followed by the retina service at our institution who were treated with systemic belzutifan. Patient age, gender, genotype, presence of systemic tumors, indication for the drug, initial dose, adjusted dose, side effects, and tumor response were recorded. We also conducted a literature search for all manuscripts describing the effect of belzutifan on VHL-associated ocular tumors. Results: We identified 12 eyes of 7 patients with VHL-associated ocular tumors who were treated with belzutifan at our institution. Of these, 5 eyes of 3 patients had progressing ocular tumors when belzutifan was started. Of the 7 total patients, 2 were treated for renal cell carcinoma, 2 for CNS hemangioblastomas, 2 for RH, and one for pancreatic neuro-endocrine tumor. Initial dose was 120 mg PO daily in 6 patients and 80 mg PO daily in one patient. The dose was reduced in all but one patient due to side effects. The ocular tumors were controlled in all patients with average follow up of 13 months (range 4-24 months). Literature review identified 7 manuscripts that described belzutifan-mediated control of ocular tumors in patients with VHL-associated RH in 21 patients. Conclusion: The drug belzutifan shows great promise for controlling RH and preventing vision loss in patients with VHL. Further work needs to address the optimal dose, role of the drug as a neo-adjuvant therapy, and long-term efficacy and tolerability of the drug in a larger cohort of patients with ocular tumors.

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The road to systemic therapy in von Hippel-Lindau (VHL) disease: Are we there yet?

Cited by 5 publications

References 40 publications

Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort

Combining germline, tissue and liquid biopsy analysis by comprehensive genomic profiling to improve the yield of actionable variants in a real-world cancer cohort

Stereotactic Radiosurgery for Hemangioblastomas

Belzutifan in Individuals with von Hippel-Lindau Retinal Hemangioblastomas: Institutional Experience and Review of the Literature

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